In mass spectrometry, it is often useful to calibrate spectrometer instruments using a reference mass, which, since its mass is accurately known, can be used to compensate for drifting of the mass assignments. Reference masses are typically introduced into the ion source section where they can sometimes interfere with analyte ion production or otherwise complicate the design and ease of use of the analyte ion source. For example, in electrospray (ESI and nano ESI) sources, a dual sprayer inlet is used, requiring extra components and constraining interchangeability of the source modules. With regard to APCI, APPI and multimode sources, reference masses are typically added directly to the analyte stream which can result in signal suppression and precipitation. In AP-MALDI sources, ions are spiked into the matrix. This approach suffers from ion suppression of the reference masses or analytes embedded in the matrix. Furthermore, with regard generally to all techniques of introducing of reference masses at the analyte ion source stage, additional instruction for customers and additional development for manufacturers is often required for proper operation.